Integrative Analysis Identifies a Novel AXL-PI3 Kinase-PD-L1 Signaling Axis Associated with Radiation Resistance in Head and Neck Cancer.

The primary cause of death due to head and neck squamous cell carcinoma (HNSCC) is local treatment failure. The goal of this study was to examine this phenomenon using an unbiased approach. We utilized human papilloma virus (HPV)-negative cell lines rendered radiation-resistant (RR) via repeated exposure to radiation, a panel of HPV-negative HNSCC cell lines and three cohorts of HPV-negative HNSCC tumors ( = 68, 97, and 114) from patients treated with radiotherapy and subjected to genomic, transcriptomic, and proteomic analysis.

Down-regulation of malic enzyme 1 and 2: Sensitizing head and neck squamous cell carcinoma cells to therapy-induced senescence.

Background: The purpose of this study was to present the results of our investigation of malic enzyme (ME) expression and the induction of senescence in head and neck squamous cell carcinoma (HNSCC).

Methods: P53, ME1, ME2, and aspects of cellular metabolism, such as reactive oxygen species (ROS) were investigated in HNSCC cell lines.

Results: Both metformin and ionizing radiation inhibited the expression of ME2, but not ME1, in HNSCC.

The p53-reactivating small molecule RITA induces senescence in head and neck cancer cells.

TP53 is the most commonly mutated gene in head and neck cancer (HNSCC), with mutations being associated with resistance to conventional therapy. Restoring normal p53 function has previously been investigated via the use of RITA (reactivation of p53 and induction of tumor cell apoptosis), a small molecule that induces a conformational change in p53, leading to activation of its downstream targets. In the current study we found that RITA indeed exerts significant effects in HNSCC cells.